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Biomedical subjects

A N Kingsnorth

Publications and source records attributed to A N Kingsnorth.

At least 19 recordsLinked to original sources
PubMed1999

Glucagonoma syndrome: survival 24 years following diagnosis.

The symptoms of necrolytic migratory erythema, diabetes, stomatitis, weight loss and diarrhoea represent the glucagonoma syndrome which has been recognized since the early 1970s. Because of its rarity (1 case/20-200 million population) late diagnosis is frequent which leads to a poor prognosis. The case described, originally reported in 1974, is the longest survivor to be documented in the literature, and is one of the original patients with a glucagonoma that helped to define the syndrome.

Aged↗
PubMed1999

Teleteaching--a practical and economical method of delivering surgical education.

The Plymouth Regional MRCS Course was initiated in 1997 to support the College STEP learning course and supplement the BST clinical training programmes. The course is a comprehensive fortnightly day-release scheme, covering, over one year in 21 full days of teaching, the entire MRCS syllabus in a structured programme of learning.

Education, Distance↗
PubMed1998

Audit of patient outcomes after herniorrhaphy.

The efficacy of a surgical procedure is a measure of outcome when performed by specialists. The monotonous excellence of countless cohort studies bears witness to the efficacy of numerous techniques of herniorrhaphy. Effectiveness, however, is of far greater relevance to health care commissioners than efficacy. Audit is an instrument of effectiveness and can be further developed to study cost-effectiveness where outcomes do not differ greatly.

Ambulatory Surgical Procedures↗
PubMed1998

Allelotype analysis of oesophageal adenocarcinoma: loss of heterozygosity occurs at multiple sites.

Deletions of tumour-suppressor genes can be detected by loss of heterozygosity (LOH) studies, which were performed on 23 cases of adenocarcinoma of the oesophagus, using 120 microsatellite primers covering all non-acrocentric autosomal chromosome arms. The chromosomal arms most frequently demonstrating LOH were 3p (64% of tumours), 5q (45%), 9p (52%), 11p (61%), 13q (50%), 17p (96%), 17q (55%) and 18q (70%). LOH on 3p, 9p, 13q, 17p and 18q occurred mainly within the loci of the VHL, CDKN2, Rb, TP53 and DCC tumour-suppressor genes respectively. LOH on 5q occurred at the sites of the MSH3 mismatch repair gene and the APC tumour-suppressor gene. 11p15.5 and 17q25-qter represented areas of greatest LOH on chromosomes 11p and 17q, and are putative sites of novel tumour-suppressor genes. LOH on 9p was significantly associated with LOH on 5q, and tumours demonstrating LOH at both the CDKN2 (9p21) and MSH3 (5q11-q12) genes had a significantly higher fractional allele loss than those retaining heterozygosity at these sites. Six of nine carcinomas displaying microsatellite alterations also demonstrated LOH at CDKN2, which may be associated with widespread genomic instability. Overall, there are nine sites of LOH associated with oesophageal adenocarcinoma.

Adenocarcinoma↗
PubMed1997

Randomised trial of octreotide for long term management of cirrhosis after variceal haemorrhage.

OBJECTIVE: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. DESIGN: Randomised clinical trial. SETTING: University hospital. SUBJECTS: 32 patients with cirrhotic portal hypertension. INTERVENTIONS: Programmed injection sclerotherapy with subcutaneous octreotide 50 micrograms twice daily for 6 months, or programmed injection sclerotherapy alone. MAIN OUTCOME MEASURES: Episodes of recurrent variceal bleeding and survival. RESULTS: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P = 0.037, Fisher's exact test), and their survival was significantly improved (P < 0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease -6.0 mm Hg, interquartile range -10 to -4.75 mm Hg, P = 0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. CONCLUSION: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension.

Acute Disease↗
PubMed1997

Prospective study of CAM 17.1/WGA mucin assay for serological diagnosis of pancreatic cancer.

BACKGROUND: Serological tests for pancreatic cancer are little used, partly because such assays have proved insufficiently specific for screening. However, retrospective studies have reported results that compare well with commonly used scanning techniques. In this prospective study we assessed a new type of combined lectin/antibody enzyme-linked mucin assay, CAM 17.1, in a routine clinical setting. METHODS: Clinicians at a 1200-bed teaching hospital were encouraged to request the CAM 17.1 assay for any patient whose differential diagnosis included pancreatic cancer. Serum samples from 250 patients were tested during an 18-month period. Patients were followed up for at least 8 months. 75 patients who did not have symptoms of pancreatic cancer and had alternative diagnoses were also studied as a control group. FINDINGS: Of the 250 patients, 36 had pancreatic cancer, as defined by histological and imaging criteria, and eight of these patients had a resectable tumour. The sensitivity and specificity of the CAM 17.1 assay were 86% and 91%, respectively, in all patients, 85% and 81% in those who presented with jaundice, and 89% and 94% in patients who did not have jaundice. The sensitivity of the assay compared well with that of ultrasound scanning (59%) and computed tomography (83%) in these patients. Use of the CAM 17.1 assay in combination with ultrasonography allowed identification of 94% of patients with pancreatic tumours and all of those with resectable tumours. CAM 17.1 binding activity did not correlate with tumour size. INTERPRETATION: Our study confirms the usefulness of the CAM 17.1 tumour-marker assay for the diagnosis of pancreatic cancer. Serological mucin assays should be used more widely in combination with ultrasonography in the investigation of non-jaundiced patients with unexplained abdominal pain or weight loss.

Antibodies, Monoclonal↗
PubMed1997

Helicobacter pylori colonization of Barrett's esophagus and its progression to cancer.

Helicobacter pylori (HP) plays a crucial role in gastric carcinogenesis. Few studies have looked at the relationship between HP and Barrett's esophagus/cancer. To further investigate this, a study comparing the prevalence of HP and increasing grades of dysplasia was undertaken. Biopsies from 19 malignant and 94 benign cases of Barrett's esophagus were analysed histologically for the presence of HP. 34% of non-dysplastic Barrett's epithelium was colonized with HP compared with only 17% of dysplastic/malignant cases (P = 0.04). No relationship was found between HP status and: (i) length of Barrett's esophagus; (ii) the presence of ulcers or strictures; and (iii) previous anti-reflux surgery. HP colonization of Barrett's esophagus is not uncommon. We found that HP has a negative correlation with increasing dysplasia which is analogous to gastric carcinogenesis. This finding should be investigated in prospective studies to elucidate its role in Barrett's adenocarcinoma.

Adenocarcinoma↗
PubMed1997

A multicentre randomised trial comparing octreotide and injection sclerotherapy in the management and outcome of acute variceal haemorrhage.

BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.

Acute Disease↗
PubMed1997

Surgery for periampullary and pancreatic carcinoma: a Liverpool experience.

The development of a single-surgeon specialist referral practice for pancreatic surgery which evolved over an 8 year period is described. Source of referral, protocol for patient management, and operative strategy are outlined. Preoperative endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy, and stent placement where possible (85% of cases), high-resolution contrast-enhanced CT and standard pylorus-preserving pancreaticoduodenectomy with a unique reconstructive technique were employed. In 105 patients receiving curative resection for pancreatic or periampullary tumours, the overall operative mortality was 4.8% and overall morbidity 26%. Actuarial 5-year survival rates were 11% for pancreatic carcinoma and 34% for ampullary carcinoma. Resectability rate was 81% without the use of time-consuming and expensive imaging techniques for staging such as laparoscopy, intraoperative ultrasound or laparoscopic ultrasound. No specific regimen of perioperative chemoirradiation was utilised over the study period. To achieve comparable results it is recommended that patients should be referred to regional specialist surgeons in whose hands mortality and morbidity is low, costs reduced and training of pancreatic surgeons can be undertaken.

Adult↗
PubMed1996

Lung injury in the microembolic model of acute pancreatitis and amelioration by lexipafant (BB-882), a platelet-activating factor antagonist.

Acute pancreatitis is associated with the development of pulmonary dysfunction in a number of patients. The aim of this study was to determine whether acute lung injury was a feature of the microembolic model of pancreatitis in rats and to assess the therapeutic effect of lexipafant (BB-882), a potent platelet-activating factor antagonist, on the lung injury. Acute pancreatitis was induced by microembolisation of the pancreas with 20-microns polystyrene microspheres. After 12 h tissue capillary permeability was assessed by an Evans blue dye (EBD) extravasation technique and compared with that in control animals. A further group of animals received an intraperitoneal injection of BB-882 (5 mg/kg) 30 min after the induction of pancreatitis. There was a significantly increased tissue content of EBD in the pancreas and lungs of the group of animals with acute pancreatitis (p < 0.05). BB-882 ameliorated the pulmonary changes when administered after the induction of pancreatitis, as demonstrated by a significant reduction in the EBD content of the lungs (p < 0.01). Increased pulmonary vascular permeability is an early feature of the microembolic model of acute pancreatitis and these changes appear to be modified by the administration of BB-882, providing further evidence for the potential role of platelet-activating factor antagonists in the treatment of acute pancreatitis and its complications.

Acute Disease↗
PubMed1996

Cost effectiveness of detecting Barrett's cancer.

BACKGROUND: Screening Barrett's oesophagus is controversial owing to a large variation in the reported incidence of neoplastic change and lack of evidence that screening improves tumour prognosis. AIMS: To determine the incidence of Barrett's cancer, its cost of detection, and stage of disease at time of diagnosis. PATIENTS AND METHODS: Data from our surveillance programme have been reviewed to assess the incidence of malignant change, tumour stage at diagnosis, and the cost per cancer detected. RESULTS: 166 patients had annual endoscopic surveillance. Six patients (five men) developed cancer-an incidence of one cancer per 59 male and 167 female patient-years of follow up. The screened group had a significantly earlier stage than a control group of unscreened cancers (p < 0.05). The cost of detecting one cancer was Pounds 14 868 for men and Pounds 42 084 for women. CONCLUSIONS: The cost of screening for Barrett's cancer is high but may be justified on the basis of the high incidence of detecting early stage disease.

Adult↗
PubMed1996

Acute pancreatitis: assessment and management.

In the 1920s Moynihan described acute pancreatitis as "..the most terrible of all intra-abdominal calamities". He established a practice of immediate surgical intervention to remove the toxic products accumulating in the peritoneal cavity, and this treatment was endorsed by most centres, remaining the standard therapy for the next 20 years. In the 1940s, the mortality of patients treated surgically was shown to be far higher than those treated conservatively, and a more conservative line of management was recommended, comprising nasogastric stomach decompression, intravenous fluid therapy, opiate analgesia, and the administration of atropine. Despite half a century passing, a clinician would not be criticised for adopting such a regime today, which in part reflects the lack of understanding of this condition and the failure of seemingly appropriate therapy. Reduction in mortality is a consequence of advances in intensive care preventing the high early mortality of organ failure, but the area of specific therapy remains elusive. While this is so, the mortality rates for these patients will remain static, while the doctor continues to feel clinically impotent.

Acute Disease↗
PubMed1996

Octreotide in the control of post-sclerotherapy bleeding from oesophageal varices, ulcers and oesophagitis.

Bleeding from oesophageal varices, oesophageal ulcers or oesophagitis is occasionally massive and difficult to control. Octreotide, a synthetic analogue of somatostin lowers portal pressure and collateral blood flow including that through varices, increases lower oesophageal sphincter pressure, and inhibits the gastric secretion of acid as well as pepsin. Our current experience suggests it is effective in controlling acute variceal haemorrhage. Therefore we have examined the efficacy of octreotide in the control of post-sclerotherapy bleeding from oesophageal varices, oesophageal ulcers and oesophagitis. During the study period 77 patients experienced a significant gastrointestinal bleed (blood pressure < 100 mm Hg, pulse > 100 beats per min or the need to transfuse 2 or more units of blood to restore the hemoglobin level) following injection sclerotherapy of oesophageal varices. The source of bleeding was varices in 42 patients, oesophageal ulcers in 31 and oesophagitis in 4. All patients received a continuous intravenous infusion of octreotide (50 micrograms/h) for between 40-140h. If bleeding was not controlled in the first 12h after commencing octreotide hourly bolus doses (50 micrograms) for 24h were superimposed on the continuous infusion. Haemorrhage was successfully controlled by an infusion of octreotide in 38 of the 42 patients with bleeding from varices, in 30 of 31 patients with oesophageal ulceration, and all patients with oesophagitis. In the 1 patient with persistent bleeding from oesophageal ulceration and in 2 of the 4 with continued haemorrhage from varices, haemostasis was achieved by hourly boluses of 50 micrograms octreotide for 24h in addition to the continuous infusion. No major complications were associated with octreotide administration. The results of this study clearly indicate that octreotide is a safe and effective treatment for the control of severe haemorrhage after technically successful injection of sclerotherapy.

Adult↗
PubMed1996

Platelet-activating factor.

Platelet-activating factor (PAF) is a proinflammatory lipid. It has been strongly implicated in the regulation of pancreatic exocrine secretion and in the local and systemic events which occur in acute pancreatitis. PAF antagonists, when given as pretreatment, ameliorate the severity of experimental acute pancreatitis by reducing serum amylase, oxidative injury, morphological changes, polymorph infiltration, pulmonary damage, and exudative levels of PAF in blood and peritoneal fluid. The novel, potent PAF antagonist, lexipafant, can ameliorate microvascular-induced acute pancreatitis after induction of the disease. It also reduces lung injury by preventing increased pulmonary capillary permeability. In a double-blind, randomized, Phase II, clinical study of lexipafant in human acute pancreatitis, a clinical benefit was found, as indicated by a significant reduction in an organ failure score measured during 72 h of infusion. In addition, organ failure recovered in seven of 12 severe acute pancreatitis patients treated with lexipafant, but recovered in only two of 11 patients given placebo. New organ failure developed in a further two patients on placebo. The results of these studies indicate that lexipafant is a potential therapy for the treatment of human acute pancreatitis. A multicentre, Phase III, UK study in patients with severe acute pancreatitis is currently underway.

Acute Disease↗
PubMed1995

Inflammatory mediators in acute pancreatitis.

The cellular events leading to acute pancreatitis are not well defined and the mechanism by which known aetiological factors initiate the disease process remains to be established. Inflammatory mediators have recently been implicated as potential early markers of disease severity and may help elucidate the pathophysiology of the disease. Oxidative stress is emerging as a common effector of the acinar cell injury in experimental acute pancreatitis and clinical findings indicate that neutrophil activation is a significant early event. In common with neutrophil-mediated tissue damage in states of tissue hypoperfusion, acute pancreatitis shows many features of an ischaemia-reperfusion injury. Increased levels of phospholipase A2 have been demonstrated; this enzyme induces synthesis of prostaglandins and platelet-activating factor, a potent inflammatory mediator. New therapeutic approaches to the complications of acute pancreatitis may be through manipulation of such mediators of inflammation.

Acute Disease↗